..Deciphering the mechanisms of these varied cell functions necessitates an understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action...

..These S1P receptors are differentially expressed, coupled to various G proteins, and regulate angiogenesis, vascular maturation, cardiac development and immunity, and are important for directed cell movement...

..These results also highlight the key role of SphK1 and its product S1P in TNF-alpha signalling and the canonical NF-kappaB activation pathway important in inflammatory, antiapoptotic and immune processes...

..Platelet-released Sph-1-P, linked to Rac- and Rho-dependent cytoskeletal rearrangement, may act late in angiogenesis to stabilize newly formed vessels, which often display abnormally increased vascular permeability...

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two of the best-studied lysophospholipids, are known to influence diverse biological events, including organismal development as well as function and pathogenesis within ..

..This process depended on the same pH gradient that exists across endosome membranes in vivo and was selectively controlled by Alix. In turn, Alix regulated the organization of LBPA-containing endosomes in vivo...

Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells

..under alkaline and acidic conditions), capable of detecting Sph-1-P, LPA, and possibly structurally similar lysophospholipids, whereby a marked formation of [(32)P]Sph-1-P, but not [(32)P]LPA, was observed in [(32)P]orthophosphate-..

..The HDL-C-normalized plasma level of S1P is increased in sCAD and even further in MI. This may be caused by an uptake defect of HDL for plasma S1P in CAD, and may represent a novel marker of HDL dysfunction...

..In summary, our results suggest that the expression of both LPA1 and LPA2 may contribute to chemotaxis and may permit cells to respond optimally to a wider range of LPA concentrations, thus revealing a new aspect of LPA signaling...

..We hypothesized that some of the cholesterol transport-independent biological properties of high-density lipoprotein (HDL) implied in atheroprotection may also be beneficial in settings of acute myocardial reperfusion injury...

..However, the cellular mechanism by which HDL exerts antiatherogenic actions is not well understood. In this study, we focus on the lipid components of HDL as mediators of the lipoprotein-induced antiatherogenic actions...

..Our data emphasize distinct mechanisms regulating the circulation of various lymphocyte subsets and raise the possibility that NK cell trafficking may be manipulated by therapies specifically targeting S1P5...

Plasma lipoproteins behave as carriers of extracellular sphingosine 1-phosphate: is this an atherogenic mediator or an anti-atherogenic mediator?

..From an evolutionary perspective, S1P receptors may have co-evolved with the advent of a closed vascular system and the trafficking paradigms for hematopoietic cells to navigate in and out of the vascular system...

..The extracellular effect appears to have a primary role in S1P-evoked cell motility. The data suggest S1P sensing by TRPC5 calcium channel is a mechanism contributing to vascular smooth muscle adaptation...

..Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, regulates the function of numerous cell types. In this study, we determined the role of S1P in promoting pro-fibrotic actions of cardiac fibroblasts (CFs)...

..Thus, LPA could be a potential target for cancer therapy. This review summarizes evidence that implicates LPA in the pathophysiology of human ovarian cancer and likely other types of human malignancies...

..In addition, small molecule agonists and antagonists have been reported. Here we review recent data on the nervous system functions of LPA signaling, and summarize data on reported agonists and antagonists of LPA receptors...

..Adoptively transferred S1P-loaded and unloaded mouse erythrocytes displayed a normal life span and similar S1P levels 24 h after recovery, indicating that S1P incorporation and release are dynamically regulated in vivo...

..We have investigated modulating the composition of rHDL as a means of expanding its function and potential cardioprotective effects...

Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to

..We conclude and propose a new paradigm that S1P is a crucial chemoattractant for BM-residing HSPCs and that CC through MAC induces the release of S1P from erythrocytes for optimal egress/mobilization of HSPCs...

Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility

..SphK1-overexpressing PC-3 cells implanted in animals developed remarkably larger tumors and resistance to docetaxel treatment. These results provide the first in vivo demonstration of SphK1 as a sensor of chemotherapy...

Mohammad TauseefDepartment of Pharmacology and Center for Lung and Vascular Biology, College of Medicine, University of Illinois, Chicago, IL 60612, USACirc Res 103:1164-72. 2008

..Our results suggest the crucial role of activation of the SPHK1-->S1P-->S1P1 signaling pathway in response to inflammatory mediators in endothelial cells in regulating endothelial barrier homeostasis...

..In addition to this, detailed biochemical studies of phospholipid and lysophospholipids can be pursued that will reveal basic biochemical mechanisms of lipid biochemistry not previously considered...

..This proposal builds upon a recently reported link between a lipid signaling system and FH: lysophospholipids (LPs) that include LPA (lysophosphatidic acid), S1P (sphingosine 1-phosphate), and other related LPs...

..activity of lysophospholipase(s) in platelets and neutrophils, and how these enzymes may regulate levels of lysophospholipids, which are lytic to cells but can be utilized as substrate for formation of new phospholipids; 3) presence ..

..thrombin stimulation of endothelial cells results in the activation of iPLA2 and the release of choline lysophospholipids. If these metabolites gain access to the ventricular myocyte sarcolemma, they may also contribute to ..

..sPLA2-mediated surfactant dysfunction will be the result of multiple mechanisms including: generation of lysophospholipids and unsaturated fatty acids, conversion of large functional surfactant aggregates to small dysfunctional ..

..will cover: 1) the biochemistry of generation and degradation of biologically active eicosanoids and lysophospholipids; 2) new knowledge of receptors, signal transduction pathways and mechanisms of regulation of cellular ..

..It is notable that the small size of these lipid molecules makes them attractive targets for drug design, and results from this proposal could serve as a foundation for new therapies based upon lysophospholipid-mimetic drugs. ..

..In toto, the studies proposed in this grant will increase the knowledge about pathogenesis of AIDS associated thrombocytopenia and may lead to development of new strategies for its treatment of prevention. (End of Abstract) ..

..Worldwide current and future clinical trials will be discussed. Short papers on the workshop topics, future directions, and scientific updates will be published via Internet and summary papers in peer-reviewed journals. ..

..Fourth, these new materials will be evaluated for cytocompatibility and cell growth in vitro with murine fibroblasts. Finally, selected materials will be seeded with fibroblasts and injected into nude mice for in vivo tissue generation. ..